Back to Search
Start Over
Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing.
- Source :
-
Clinical and experimental nephrology [Clin Exp Nephrol] 2017 Feb; Vol. 21 (1), pp. 136-142. Date of Electronic Publication: 2016 Mar 11. - Publication Year :
- 2017
-
Abstract
- Background: Nephronophthisis-related ciliopathies (NPHP-RC) are a frequent cause of renal failure for children and adolescents. Although diagnosing these diseases clinically is difficult, a comprehensive genetic screening approach of targeted resequencing can uncover the genetic background in this complicated family of diseases.<br />Methods: We studied three Japanese female patients with renal insufficiency from non-consanguineous parents. A renal biopsy for clinical reasons was not performed. Therefore, we did not know the diagnosis of these patients from a clinical aspect. We performed comprehensive genetic analysis using the TruSight One Sequencing Panel next generation sequencing technique.<br />Results: We identified three different rare NPHP-RC variants in the following genes: SDCCAG8, MKKS, and WDR35. Patient 1 with SDCCAG8 homozygous deletions showed no ciliopathy-specific extrarenal manifestations, such as retinitis pigmentosa or polydactyly prior to genetic analysis. Patient 2 with a MKKS splice site homozygous mutation and a subsequent 39-amino acid deletion in the substrate-binding apical domain, had clinical symptoms of Bardet-Biedl syndrome. She and her deceased elder brother had severe renal insufficiency soon after birth. Patient 3 with a compound heterozygous WDR35 mutation had ocular coloboma and intellectual disability.<br />Conclusions: Our results suggest that a comprehensive genetic screening system using target resequencing is useful and non-invasive for the diagnosis of patients with an unknown cause of pediatric end-stage renal disease.
- Subjects :
- Adolescent
Adult
Child, Preschool
Ciliopathies diagnosis
Consanguinity
Cytoskeletal Proteins
Disease Progression
Female
Genetic Markers
Genetic Predisposition to Disease
Hedgehog Proteins
Heterozygote
Homozygote
Humans
Intracellular Signaling Peptides and Proteins
Kidney Diseases diagnosis
Kidney Failure, Chronic diagnosis
Kidney Failure, Chronic genetics
Magnetic Resonance Imaging
Phenotype
Predictive Value of Tests
Autoantigens genetics
Ciliopathies genetics
DNA Mutational Analysis
Genetic Testing methods
Group II Chaperonins genetics
High-Throughput Nucleotide Sequencing
Kidney Diseases genetics
Neoplasm Proteins genetics
Proteins genetics
Sequence Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 1437-7799
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical and experimental nephrology
- Publication Type :
- Academic Journal
- Accession number :
- 26968886
- Full Text :
- https://doi.org/10.1007/s10157-016-1256-x